Diabetes mellitus causes widespread microangiopathy, including glomerular mesangial sclerosis resulting in progressive renal failure. Initially, we found that smooth muscle contractile protein (myosin) is greatly increased in the mesangium of diabetic kidneys, a phenomenon different from other renal disease. We found that a similar lesion develops in the previously normal kidneys transplanted into human diabetic hosts. Further, rats with streptozotocin-induced diabetes develop similar lesions. We also found that the myosin localized by immunofluorescence in the glomerular mesangium has a species specificity lacking in the myosin of arterial walls. To investigate these findings and bring them closer to an explanation of the vascular disease of diabetes, we plan to isolate the myosin from vascular walls and glomeruli, and characterize it by physiologic (ATP'ase) and immunochemical techniques. Thus, tissue-specific myosins can be compared to those of diabetic patients, determining whether a defective myosin is diffusely present in diabetic tissues, or whether a normal myosin, organized into a functioning contractile system, is hypertrophied in diabetes to result in abnormal glomerular perfusion and filtration.